Viral infection (and cancer)
All cells containing nuclei can be infected by virus. The inserted genetic material from the virus codes for the de novo synthesis of peptides eventually incorporated into new viral particles. Some of these peptides are presented to cytotoxic T cells (Tc) through MHC class I (MHC I) molecules present on almost all cells. Tc, together with natural killer cells (NK), kill the virus-infected cell. This is in contrast to what happens in bacterial or protozoal infections where antigenic peptides are generated by degradation of the microbes in phagocytic cells; see bacterial infections. Some cancer cells originate from viral infections, others do not. Many cancer cells express tumor-associated antigens generated de novo and they therefore present these peptides to Tc through MHC I molecules.
A set of cell membrane molecules on antigen-presenting cells (e.g. MØ, virus-infected cells, or certain cancer cells) seems to decide whether the specifically reactive Th or Tc (the latter is shown above) become activated or paralyzed. The molecule, CD86 (B7-2), on the antigen-presenting cell must bind to a membrane molecule, CD28, on the chosen Th or Tc cell in order to activate the cell for example to cytokine production. Hence,
...the 1. activating signal is the one generated through the specifically reactive T cell receptor (TCR) reacting with specific antigen coupled to MHC II in the case of Th cells and MHC I in the case of Tc cells (shown above);
...the 2. activating signal is generated through the CD86-CD28 bimolecular reaction.
If the B7 molecule is absent from the antigen-presenting cell, or if the chosen Th or Tc cell is dominated by another partner molecule, CD152 (CTLA-4) which binds CD80 (B7-1), a paralytic signal is generated to the T cell, and the cell becomes immunological tolerant; i.e. incapable of reacting now and at a later stage to the same antigen.
Killing mechanisms: see Apoptosis
